The present invention relates to devices, methods and systems for low volume microarray processing.
Microarrays may be used in a variety of processes, such as gene sequencing, monitoring gene expression, gene mapping, bacterial identification, drug discovery, combinatorial chemistry, etc. Many of these applications involve expensive and/or difficult to obtain analyte samples and/or reagents. Dilution of minute analyte samples to higher volumes for processing can be problematic. For example, dilution of minute quantities of the analyte sample to higher volumes can result in concentrations that may be either difficult to detect or that require inordinately long processing times.
Accordingly, microarrays are desirable because the use of such arrays may allow for lower volumes of analyte sample. Processing with a microarray may involve, for example, placing a small drop of analyte sample (e.g., 10-20 microliters) on the microarray, followed by distribution of the analyte sample over the microarray surface by addition of a coverslip. The coverslip provides both compressive weight and capillary forces in the gap between the coverslip and the microarray surface that distribute the analyte sample over the microarray surface. Those same capillary forces, however, typically prevent mixing or even distribution of the analyte sample over the microarray surface—working instead to limit diffusion of analyte molecules over the microarray surface.
One approach to addressing the issue of diffusion or mixing of the analyte sample over the microarray surface involves the use of pumping mechanisms. This approach is not, however, without its own disadvantages. For example, to obtain a volume sufficient for pumping, the analyte sample volume may need to be increased by the use of additional analyte sample or dilution of a given amount of analyte sample. In addition, the pumping mechanisms increase the complexity of the processing systems. Furthermore, in some systems that employ pumps, further agitation of the analyte sample on the microarray is performed by use of a vortexer (similar to paint mixer) in an attempt to provide adequate diffusion of the analyte molecules over the microarray surface.
Another potential disadvantage of systems employing pumps to obtain diffusion of target molecules is that the microarray surface must typically be enclosed within a sealed chamber to contain the analyte sample during pumping and/or agitation. As a result, the microarray devices must typically be designed for use in a package that can provide the needed sealed chamber. That packaging further adds to the cost and complexity of the microarrays.
Yet another potential disadvantage of sealed chambers used to package the microarrays is the formation of fluid retention interfaces within the chamber at, e.g., the junction of walls and other corners where the surface tension of the fluids results in fluid retention. The retained fluid is not capable of distribution across the surface of the microarray.